Ginsenoside Rh2-Based Multifunctional Liposomes for Advanced Breast Cancer Therapy

Abstract

Background

Most solid tumors are not diagnosed and treated until the advanced stage, in which tumors have shaped mature self-protective power, leading to off-target drugs and nanomedicines. In the present studies, we established a more realistic large tumor model to test the antitumor activity of a multifunctional ginsenoside Rh2-based liposome system (Rh2-lipo) on advanced breast cancer.

Methods

Both cholesterol and PEG were substituted by Rh2 to prepare the Rh2-lipo using ethanol-water system and characterized. The effects of Rh2-lipo on cell uptake, penetration of the tumor spheroid, cytotoxicity assay was investigated with 4T1 breast cancer cells and L929 fibroblast cells. The 4T1 orthotopic-bearing large tumor model was established to study the targeting effect of Rh2-lipo and inhibitory effect of paclitaxel loaded Rh2-lipo (PTX-Rh2-lipo) on advanced breast tumors.

Results

Rh2-lipo exhibit many advantages that address the limitations of current liposome formulations against large tumors, such as enhanced uptake in TAFs and tumor cells, high targeting and penetration capacity, cytotoxicity against TAFs, normalization of the vessel network, and depletion of stromal collagen. In in vivo study, PTX-Rh2-lipo effectively inhibiting the growth of advanced breast tumors and outperformed most reported PTX formulations, including Lipusu^® and Abraxane^®.

Conclusion

Rh2-lipo have improved drug delivery efficiency and antitumor efficacy in advanced breast cancer, which offers a novel promising platform for advanced tumor therapy.

Graphical Abstract

Keywords:

• nanomedicine
• tumor microenvironment
• chemotherapy
• tumor-associated fibroblast

Disclosure

Co-authors Dan Wang and Huaxing Zhan are employed by Xiamen Ginposome Pharmaceutical Co., Ltd. Co-author Xinnan Jiang is employed by Shanghai Jahwa United Co., Ltd. The other authors have no conflicts of interest in this work.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 82074277), and the Development Project of Shanghai Peak Disciplines-Integrated Medicine (No. 20180101).